Retroviruses, long associated with leukemias and sarcomas of animals, have recently been implicated as the etiological agent of simiam acquired immune deficiency syndrome (SAIDS), human T cell leukemias, and human acquired immune deficiency syndrome (AIDS). The identification of these agents makes it possible to consider various ways of prevention. The most promising approach is development of a vaccine that could be administered to individuals at risk. The vaccinia vector system will be evaluated because it has been shown to produce both humoral and cell mediated immunity against a variety of infectious agents. Since human retroviruses have not yet been shown to produce disease in animals, initial vaccine work must be done with animal retroviruses. Friend leukemia virus complex is a useful model system since it produces an acute disease in adult mice which can be prevented by repeated immunization with the envelope glycoprotein. The envelope glycoprotein gene has been isolated and is being engineering for expression in a live vaccinia virus vector. The ability of this recombinant vaccine to protect mice will be examined. The vaccinia virus vector system has been supplied to Cetus for development of a vaccine against feline leukemia virus, which causes immune deficiency disease in cats. Similarly, the envelope glycoprotein gene of SAIDS virus is being isolated for expression in vaccinia virus. The envelope glycoprotein gene of human AIDS viruses (HTLVIII/LAV) will be used when it becomes available